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A Multi-Center, Open-Label Study

This study has been withdrawn prior to enrollment.
Sponsor:
Information provided by (Responsible Party):
Chelsea Therapeutics
ClinicalTrials.gov Identifier:
NCT01468259
First received: November 3, 2011
Last updated: March 27, 2013
Last verified: March 2013
History of Changes
  Purpose

This study will be an open-label, single-treatment, single-dose, parallel group study to evaluate the pharmacokinetics (PK) of droxidopa in subjects with mild, moderate, and severe renal dysfunction and End Stage Renal Disease (ESRD) after a single dose compared to matched healthy subjects with normal renal function.

A total of 48 male or female subjects, 16 subjects with normal renal function (eGFR greater than 90 mL/min/1.73m²) and eight each (8) with mild (60 less than eGFR less than 89 mL/min/1.73m²), moderate (30 less than eGFR less than 59 mL/min/1.73m²), or severe (15 less than eGFR less than 29 mL/min/1.73m²) renal impairment or ESRD (eGFR < 15 mL/min/1.73m² and requiring hemodialysis) will be selected according to the inclusion and exclusion criteria. The medical and laboratory examinations will take place within 28 days before dosing. A single dose of 600 mg of droxidopa as an investigational drug will be administered with 240 mL of water after an overnight fast (minimum 10 hours).

Blood samples for the measurement of plasma concentrations of droxidopa and metabolites including but not limited to 3-OM-DOPS, NE, vanillic acid, and protocatechuic acid will be collected before and 0, .5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 30, 36 hours after dosing for healthy volunteers and subjects with mild, moderate, and severe renal impairment and those with ESRD. For the latter, samples will be collected on both a non-hemodialysis and a hemodialysis visit.

During dialysis, samples of dialysate, from the arterial and venous sides of the dialyzer will be collected at 30-minute intervals during the dialysis period. In addition, the entire dialysate will be collected, its volume recorded, and a sample retained for the measurement of droxidopa and metabolites including but not limited to 3-OM-DOPS, NE, vanillic acid, and protocatechuic acid concentrations.

Urine samples for the measurement of urinary excretion of droxidopa and metabolites including but not limited to 3-OM-DOPS, NE, vanillic acid, and protocatechuic acid will be collected before and over the following intervals after dosing: 0 2, 2-4, 4-6, 6-8, 8-12, 12-24, and 24-36 hours for healthy volunteers and subjects with mild, moderate, and severe renal impairment.

A post-study visit with physical examination and laboratory tests will take place within seven (7) days after the last PK blood sampling.


Condition Intervention Phase
Renal Disease
End Stage Renal Disease
 Drug: Droxidopa
 Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I, Multi-Center, Open-Label Study to Examine the Pharmacokinetics of a Single Dose of Droxidopa in Subjects With Renal Impairment Compared to Healthy Volunteers

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Chelsea Therapeutics:

Primary Outcome Measures:
  • Primary Objective Pharmacokinetic profile [ Time Frame: before and 0, .5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 30, 36 hours ] [ Designated as safety issue: Yes ]

    The primary objective of this study is to evaluate the pharmacokinetics (PK) of droxidopa in subjects with mild, moderate, and severe renal dysfunction and ESRD after a single oral dose compared to matched healthy subjects with normal renal function.

    The PK parameters Cmax, Tmax, AUC(inf), CL/F, Vz/F, t½, and CLr are considered the primary parameters for evaluation.



Secondary Outcome Measures:
  • Secondary Objective Safety and tolerability [ Time Frame: before and 0, .5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 30, 36 hours ] [ Designated as safety issue: Yes ]
    The secondary objective of this study is to assess the safety and tolerability of Droxidopa in matched healthy subjects and those with mild to severe renal dysfunction and ESRD through participant AEs and laboratory measures.


Enrollment: 0
Study Start Date: October 2012
Estimated Study Completion Date: December 2012
Estimated Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Normal renal function
16 subjects with normal renal function (eGFR greater than 90 mL/min/1.73m²)
 Drug: Droxidopa
The dose to be used is a single 600 mg dose (2 x 300 mg capsules) of droxidopa.
Experimental: Mild RD
Eight (8) with mild (60 less than eGFR less than 89 mL/min/1.73m²)
 Drug: Droxidopa
The dose to be used is a single 600 mg dose (2 x 300 mg capsules) of droxidopa.
Experimental: Moderate RD
Eight with moderate (30 less than eGFR less than 59 mL/min/1.73m²),
 Drug: Droxidopa
The dose to be used is a single 600 mg dose (2 x 300 mg capsules) of droxidopa.
Experimental: Severe RD
Eight with severe (15 less than eGFR less than 29 mL/min/1.73m²)
 Drug: Droxidopa
The dose to be used is a single 600 mg dose (2 x 300 mg capsules) of droxidopa.
Experimental: End Stage Renal Disease
Eight with ESRD (eGFR < 15 mL/min/1.73m² and requiring hemodialysis)
 Drug: Droxidopa
The dose to be used is a single 600 mg dose (2 x 300 mg capsules) of droxidopa.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 79 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Informed Consent
  • Male or Female between 18 and 79 years
  • Female subject of childbearing potential not surgically sterile or min 2 years postmenopausal must use approved contraceptives
  • BMI 20 to 40 kg per m2
  • Refrain from exercise
  • eGFR per protocol for condition
  • Sufficient venous access
  • Stable medication dosing 14 days prior to and during study
  • Healthy control subjects must show good general health per protocol
  • Subjects will be matched Healthy to Renal Impaired by demographics data

Exclusion Criteria:

  • Inability to complete study
  • Insufficient venous access
  • Clinically significant illness within 4 weeks of study
  • History of clinically unstable disease except renal impairment in those subjects
  • Medical or surgical conditions that may inhibit absorption of IP
  • Laboratory value or medical issue which may interfere with study data or be hazardous for the subject
  • Medication that may interfere with drug absorption or elimination process 4 weeks prior to study
  • Consumption of grapefruit products within 7 days prior and after study
  • Dose changes of medications 14 days prior to and during study
  • Active alcohol abuse or drug addiction
  • Positive alcohol test at screening or after
  • Excessive xanthine consumption
  • Positive serology test Hepatitis B or Hepatitis C or HIV
  • Excessive nicotine usage
  • Positive urine screen for drugs of abuse without prescription
  • Clinically relevant abnormal 12 lead ECG
  • Donation of bood or plasma or platelets within 30 days of study
  • Clinical trial with another agent within 30 days or 5 half lives whichever is longer
  • Informed consent unavailable or withdrawn
  • Any condition the investigator feels would interfere with study data or subjects health
  • Employee or relative of study center or center staff or investigator
  • Any condition that may increase risk for subject
  • Clinically significant lab value
  • Clinically significant acute or chronic disease other than renal impairment in those subjects that may interfere with data or health
  • Medication dose change within 14 days of study
  • Seated BP greater than 180 over 105
  • Healthy subject with history of renal impairment
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01468259

Locations
United States, Tennessee
NOCCR
Knoxville, Tennessee, United States, 37920
Sponsors and Collaborators
Chelsea Therapeutics
Investigators
Study Director: William D Schweiterman, MD Chelsea Therapeutics
  More Information

No publications provided

Responsible Party: Chelsea Therapeutics
ClinicalTrials.gov Identifier: NCT01468259     History of Changes
Other Study ID Numbers: Droxidopa NOH103
Study First Received: November 3, 2011
Last Updated: March 27, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Kidney Diseases
Kidney Failure, Chronic
Urologic Diseases
Renal Insufficiency, Chronic
Renal Insufficiency
Droxidopa
 Antiparkinson Agents
Anti-Dyskinesia Agents
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 21, 2013